Peripheral artery disease and trauma are leading causes of morbidity and amputation in the United States. Recent advances in biomaterials provide for potential development of small diameter vascular grafts as a life-saving treatment. Development of a life-long graft (<6 mm id) requires a construct that will not cause significant blood clotting/thrombosis and allow biologic integration to sustain life-long performance. Gel-Del Technologies has developed and tested prototypes using a patented fabrication process with purified proteins, water, and other biochemicals to produce biomimetic vascular constructs (Gel-Del(R) VasoGraft""""""""). Collagen and elastin proteins, along with the anti-clotting factor, heparin, are processed together with a scaffolding material to create a tubular construct (VasoGraft""""""""). VasoGraft testing and recent SBIR Phase I and II studies demonstrate excellent bio- and hemocompatibility, including non-thrombosis, host tissue integration and in vivo patency, in tests continuing out past 150 days using a porcine femoral artery model. While the graft's lumen remains non-thrombogenic, significant intimal hyperplasia occurs in native artery anastomosis sites, an expected adverse response to surgical arterial transection. Because the graft functions well, it was hypothesized here that reduction of intimal hyperplasia allows long-term function and patency. Therefore, we have developed an additional component of the VasoGraft system, which incorporates drug (rapamycin) to inhibit smooth muscle cell proliferation in the native artery. In vitro drug elution profiles have been characterized, and incorporation of this drug-eluting component has led to increased length of graft patency in a porcine femoral artery model. This proposal will pursue the necessary steps to gain IDE approval to commence clinical trials with the VasoGraft System, including additional long-term porcine efficacy studies, biocompatibility and safety studies according to ISO 10993, and manufacturing scale-up. These studies will be executed as follows:
Aim 1 : Assess optimal dose of rapamycin within drug-eluting threads for reducing stenosis, and test this within the VasoGraft System under GLP conditions using the porcine femoral artery end-to-end anastomosis model out to 450 days. VasoGraft System will be made with scaleable manufacturing procedures.
Aim 2 : Complete manufacturing scale up, and perform biocompatibility/safety/stability testing required for IDE submission.
Aim 3 : Final preparation of IDE and submission to FDA.
These aims will generate the necessary information to submit an IDE application for approval to test the VasoGraft in a clinical trial, designed to include 30 patients with a 6-month follow-up to address any safety issues.
Peripheral vascular disease and trauma is a prevalent cause of amputation for military personnel and general population in the United States. Current blood vessel graft replacements are inadequate, often leading to occlusion and graft failure. The development of a novel blood vessel graft, which can also be utilized at trauma and battlefield sites, will greatly enhance the lives of people suffering from PAD or trauma.